Dark Proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses

Rajanish Giri; Taniya Bhardwaj; Meenakshi Shegane; Bhuvaneshwari R. Gehi; Prateek Kumar; Kundlik Gadhave

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.13.990598 doi: bioRxiv preprint SARS-CoV-2 Nsp1 shares 84.44% and 83.80% sequence identity with Nsp1s of Human SARS CoV and Bat CoV, respectively. Its N-terminal region is found to be more conserved than the rest of the protein sequence ( Figure 19E ). Mean PPIDs of Nsp1s from SARS-CoV-2, Human SARS CoV, and Bat CoV are 12.78%, 14.44%, and 12.85%, respectively. Figure 19A , 19B, and 19C represent the graphs of predicted per-residue intrinsic disorder propensity of these Nsp1s. According to the analysis, the following regions are predicted to be disordered: SARS-CoV-2 (residues 1-7 and 165-180), Human SARS CoV (residues 1-5 and 165-180), and Bat CoV (residues 1-5 and 165-179). NMR solution structure of Nsp1 from Human SARS revealed the presence of two unstructured segments near the N-terminal (1-12 residues) and C-terminal (129-179 residues) regions [125] . The disordered region residues) at C-terminus is important for Nsp1 expression [126] . Based on sequence homology with Human SARS CoV Nsp1, the predicted disordered C-terminal region of SARS-CoV-2 Nsp1 may play a critical role in its expression. Alanine mutants at K164 and H165 in the Cterminal region of Nsp1 protein is reported to abolish its binding with the 40S subunit of the host ribosome [127] . In conjunction with this data, several MoRFs are present in the unstructured segments of Nsp1 proteins. These regions are tabulated in Table 2 , and Supplementary Tables 7 and 8. author/funder. All rights reserved. No reuse allowed without permission.